Signal integration by membrane signalling assemblies

Prof. Dr. Carola Hunte (CIBSS-SpeakerTeam, CIBSS-PI), Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg

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Dynamic protein assemblies of high complexity mediate signalling processes at and across membranes. They operate as functional units and integrate signals in response to multiple external and internal stimuli. Signal integration enables precise control of cellular functions and provides the basis for the mutual regulatory interplay with cellular metabolism. Yet, an in depth knowledge of the structural basis and mechanism of signal integration is lacking.

We aim to elucidate the molecular basis and fundamental principles of signal integration through membrane bound supra-molecular assemblies, in order to understand how these functional units orchestrate cellular signalling. The project includes studies on signal integration by the human sodium/proton exchanger 1 (NHE1), a ubiquitous acid extruder of the plasma membrane, vital for precise control of intracellular pH and cell volume and thus for cell division and proliferation. Experimentally, we pursue an integrative structural biology approach that combines structural, biochemical and biophysical methods with targeted and global proteomics. The information on structure and molecular mechanism will be challenged in physiological context in cells and model organisms. Precise control of the vital functions of these assemblies is the long-term goal of the study.